Development of a number of nontricyclic antidepressants with reduced or completely diminished cardiovascular or anticholinergic liability has been reported in recent years. Among those one of the most prescribed antidepressants is venlafaxine, which is a unique drug with well documented efficacy & safety in the acute treatment of major depressive disorder. It was first time released for clinical trials in 1994 by Wyeth Company, now part of Pfizer and globally marketed as effexor R®. It has now become widely recognised as an effective first line agent in the treatment of major depressive disorder (MDD), generalized anxiety disorder, and comorbid indications in certain anxiety disorder for depression. It was a top selling drug from 2006, to 2008 and sixth most prescribed antidepressant in US in the year 2007. In 2010, it ranked 25th in top 200 brand name drugs by total US prescriptions.
Venlafaxine is marketed in racemic form, although both R & S enantiomers show different bio activities i.e. S-enantiomer is a selective serotonin reuptake inhibitor, while R enantiomer is more selective towards norepinephrine transporter. Also, it has either no or has little activity on a variety of neuroreceptors.
Article titled, “An efficient and green protocol for the preparation of cycloalkanols: a practical synthesis of venlafaxine” by Subhash P. Chavan in Tetrahedron Letters, Volume 45. Issue 39, 20 Sep. 2004, Pages 7291-7295 reports The condensation of arylacetonitriles with cyclic ketones using aqueous NaOH or KOH under phase transfer catalysis to give almost quantitative yields of cycloalkanols. This protocol is utilized for a practical synthesis of the antidepression drug, venlafaxine 1.

Article titled, “Asymmetric synthesis of both the enantiomers of antidepressant venlafaxine and its analogues” by Rajib Bhuniya, Samik Nanda in Tetrahedron Letters, Volume 53, Issue 15, 11 Apr. 2012, Pages 1990-1992 reports Chemoenzymatic asymmetric synthesis of antidepressant agent venlafaxine and its analogue. The main highlight of the reported synthesis is the stereoselective synthesis of cyanohydrins by (S)-hydroxynitrile lyase (Hevea brasiliensis) followed by lipase catalyzed kinetic resolution.

U.S. Pat. No. 6,756,502 B2 discloses a process for the preparation of Venlafaxine via the novel epoxy-nitrile intermediate,

Article titled, “Asymmetric total synthesis of (−)-venlafaxine using an organocatalyst” by Subhash P. Chavan in Tetrahedron Letters, Volume 54, Issue 17, 24 Apr. 2013, Pages 2137-2139 reports that an asymmetric total synthesis of (−)-venlafaxine using an organocatalyst has been achieved via a unified strategy employing organocatalytic Michael addition, regio-selective dehydration and selective epoxide ring opening.
US 2007/0135449 A1 discloses a process for selectively synthesising the desired enantiomer of an intermediate useful in the production of a 2-phenyl-2-(1-hydroxycycloalkyl)ethylamines of formula 1:
wherein X is OCH3 or CF3, R1 and R2 are each independently selected from C1-C3 alkyl, or together with the nitrogen they are attached from a 1,4-piperazine ring wherein said piperazine ring is substituted with from 0 to 2 methyl groups. The process of the invention comprises the steps of: treating a (4S or 4R)-4-benzyl-3-[(methoxyphenyl)acetyl]-1,3-oxazolidin-2-one having the structure
wherein X is selected from the group consisting of methoxy or trifluoromethoxy; with a base under conditions which permit formation of the corresponding anion; and mixing the corresponding anion with cyclohexanone under conditions which permit an aldol reaction to form the corresponding (4S or 4R)-4-benzyl-3-[(2R or 2S)-2-(1-hydroxycyclohexyl)-(methoxyphenyl)acetyl]-1,3-oxazolidin-2-one.
Article titled, “Simple and an efficient method for the synthesis of 1-[2-dimethylamino-1-(4-methoxy-phenyl)-ethyl]-cyclohexanol hydrochloride: (±) venlafaxine racemic mixtures” by Basappa, C. V. Kavitha, K. S. Rangappa in Bioorganic & Medicinal Chemistry Letters, Volume 14, Issue 12, 21 Jun. 2004, Pages 3279-3281 reports a novel synthetic method was developed for the synthesis of venlafaxine using inexpensive reagents.
WO 2010046808 A2 discloses a process for the preparation of Venlafaxine Hydrochloride comprising steps of i) treating 4-methoxyphenyl acetonitrile with cyclohexanone in presence of alkali hydroxide and super base to get 1-[cyano (4-methoxyphenyl) methyl] cyclohexanol and ii) reducing 1-[cyano (4-methoxyphenyl) methyl] cyclohexanol in presence of catalyst, activator and alcoholic ammonia under hydrogen pressure.
Therefore it is the need to develop an efficient process for asymmetric synthesis of venlafaxine, wherein one enantiomer is obtained in high enantiomeric purity.